The objectives of the proposed research are: (1) to determine the detailed physiochemical and conformational properties of nucleic acids and their constituents in which hydrogen atoms have been selectively replaced with fluorine atoms; (2) to determine the translation properties (using an in vitro mammalian system) of model nucleic acids containing fluoinated bases to determine their potential for miscoding; and (3) to evalute fluorinated nucleic acid constituents as nuclear magnetic resonance (NMR) probes in studying the structure and function of macromolecules in vitro. The methods include both chemical and enzymatic synthesis of the nucleotides, oligo-, poly-, and copolynucleotides to be used as model nucleic acids. These will be analyzed by ultraviolet (UV), circular dichroism (CD), and NMR spectroscopies to determine their solution properties, and selected constituents will be analyzed by X-ray diffraction to determine their solid state conformation. A mammalian in vitro protein-synthesizing system will be used to determine the extent and conditions of miscoding by synthetic fluorinated-mRNA.